dna structure and replication. pentose sugar nitrogen base phosphate group sugar base po 4 dna is a...
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DNA STRUCTURE AND REPLICATION
• pentose sugar• nitrogen base• phosphate group
Sugar
Base
PO4
DNA IS A POLYMER OF DNA IS A POLYMER OF NUCLEOTIDESNUCLEOTIDES
NUCLEOSIDESNUCLEOSIDES
SUGAR IN DNA
NITROGENOUS BASES
PURINES
Found in DNA and RNA
PYRIMIDINESPYRIMIDINES
C in DNA and RNA T in DNA, U in RNA
NUCLEOSIDE/NUCLEOTIDE NUCLEOSIDE/NUCLEOTIDE LINKAGESLINKAGES
- N- glycosidic linkage between the ribose sugar and base
NOMENCLATURENOMENCLATURE
A DNA POLY-NUCLEOTIDE
(5’ - TACG- 3’)’
BASE PAIRING
CHARGAFF’S RULE
PURINES = PYRIMIDINES
THE DNA DOUBLE HELIXTHE DNA DOUBLE HELIX
The DNA strands are anti parallel
STRUCTURAL FORMS OF THE DNA DOUBLE HELIX
A-DNA B-DNA Z-DNA
CHROMATIN CHROMATIN STRUCTURESTRUCTURE
SEPARATION OF THE DNA DOUBLE HELIX
DNA ReplicationDNA Replication
““It has not escaped our notice that the It has not escaped our notice that the specific pairing we have postulated specific pairing we have postulated
immediately suggests a possible immediately suggests a possible copying mechanism for the genetic copying mechanism for the genetic
material”material”
James Watson and Francis CrickJames Watson and Francis Crick
NatureNature, 1953, 1953
DNA Replication: Very Replication: Very Simply….Simply….
DNA Replication: DNA Replication: The ComplexitiesThe Complexities
[1]The site of initiation of replication is not chosen randomly
How does the cell know where to start replication???
Origins of replicationOrigins of replication
[2][2]
• For replication to occur, the parental DNA double helix has to be separated into single strands
What protein is required to make the DNA single stranded during replication????
DNA helicaseDNA helicase
[3][3]• Single stranded DNA is vulnerable to damage• Normally complementary single DNA strands
reform the double helix
What proteins are required keep the DNA single stranded during replication and to protect it from damage????
SSB ProteinsSSB Proteins
• Each eukaryotic chromosome is one linear DNA double helix
• Average ~108 base pairs long• With a replication rate of 2 kb/minute,
replicating one human chromosome would require ~35 days (S phase of eukaryotic cell cycle = 6-8 hrs)
How are eukaryotic DNA molecules replicated in time????
[4][4]
Multiple Origins of replicationMultiple Origins of replication
[5][5]• The two DNA strands twist around each
other to form a helix. As the two strands are pulled apart it leads to the tightening of the twists in regions upstream of replication initiation points and the introduction of ‘supercoils’.
How are supercoils removed from the DNA helix????
SUPERCOILINGSUPERCOILING
TOPOISOMERASE ITOPOISOMERASE I
TOPOISOMERASE IITOPOISOMERASE II
[6][6]• The primary DNA replication enzyme,
DNA polymerase, can only add nucleotides to an existing strand of nucleotides i.e., it cannot start the replication process by itself.
How does replication get started????
RNA PrimerRNA Primer
[7][7]• DNA polymerase can only add
nucleotides in one direction, 5’ 3’ i.e., creation of both the new strands is in the 5’ 3’ direction
• However, the two DNA strands are antiparallel to each other --- one runs 5’ 3’ and the other 3’ 5’. Both strands have to be replicated. How is the problem of directionality solved????
[8][8]
• The solution to problems 6 requires the excision of RNA primers and their replacement by DNA.
Which enzyme is involved in this step and how does it work ????
DNA polymerase IDNA polymerase I
•5’→3’ exonuclease activity•5’→3’ polymerase activity
[9][9]• The solutions to problems 7 and 8 leave
the newly synthesized DNA with single strand breaks or ‘nicks’.
Which enzyme is involved this sealing these breaks ????
[10][10]
• The mis-incorporation of a single nucleotide during replication could lead to deleterious or even lethal mutations.
How is replication fidelity maintained ????
[11]• In eukaryotes DNA polymerase cannot fill the
gaps at ends of chromosomes after RNA primer is removed.
• If this gap is not filled, chromosomes would become shorter each round of replication!
How are the telomeric regions replicated without shortening of chromosomes???
TELOMERESTELOMERES